March 12, 201512:30 PM – 1:45 PMHouston, TX

Educational Partner

Sponsored by pmiCME

Optimizing the Diagnosis, Treatment, and Management ofIrritable Bowel Syndrome

Session 4

Session 4: Optimizing the Diagnosis, Treatment, and Management of Irritable Bowel Syndrome Learning Objectives

1. Diagnose IBS and differentiate from other bowel disorders using established clinical guidelines. 2. Summarize the efficacy and safety of pharmacologic and nonpharmacologic treatment options for IBS. 3. Implement patient-specific methods for managing IBS symptoms and improving function and quality of life.

Faculty

Brooks D. Cash, MD Professor of Medicine University of South Alabama Mobile, Alabama Dr Brooks Cash is a professor of medicine at the University of South Alabama (USA), Mobile, Alabama; where he has held a faculty position since 2013. He was previously a professor of medicine at the Uniformed Services University of the Health Sciences, Bethesda, Maryland. He currently serves as the director of the motility and physiology service at the USA Digestive Health Center. Prior to his relocation to USA, Dr Cash served in the United States Navy for 24 years, retiring in 2013 at the rank

of captain, as the deputy commander for medicine at Walter Reed National Military Medical Center, Bethesda, Maryland. Dr Cash received his undergraduate degree in business administration (finance) with honors from The University of Texas at Austin. He earned his medical degree from the Uniformed Services University of Health Sciences and completed his internship, residency, and gastroenterology fellowship at the National Naval Medical Center, Bethesda. Dr Cash is a diplomate of the American Board of Gastroenterology. He is a fellow of the American College of Physicians, American College of Gastroenterology (ACG), American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. Dr Cash serves on the Rome Foundation committee for functional gastrointestinal disorders and has authored multiple articles and book chapters on a variety of gastrointestinal topics, including irritable bowel syndrome and chronic constipation, colorectal cancer screening, CT colonography, acid peptic disorders, Barrett esophagus, and evidence based medicine. He serves as an associate editor for The American Journal of Gastroenterology and is an editorial board member and reviewer for numerous internal medicine and gastroenterology medical journals. Dr Cash most recently served as the governor of ACG’s military region.

Spencer Dorn, MD, MPH, MHA Vice Chief Gastroenterology Assistant Professor of Medicine University of North Carolina Chapel Hill, North Carolina Dr Spencer Dorn works to improve quality of care, operational efficiency, and patient experiences as vice chief of the University of North Carolina (UNC) division of gastroenterology and hepatology. As assistant professor of medicine, he conducts clinical trials for functional GI disorders, performs health services research, and examines the impact of health policy and regulations on gastroenterology. His clinical practice focuses on functional GI and motility disorders.

Dr Dorn graduated with highest distinction from the University of Michigan, Ann Arbor and summa cum laude from the State University of New York at Brooklyn College of Medicine. He earned a master of public health (epidemiology) degree and later a master of healthcare administration (health policy and management) from UNC. Dr Dorn completed his internal medicine training at Brigham and Women's Hospital, Boston, Massachusetts; where he was a clinical fellow at Harvard Medical School. He subsequently trained at UNC as a National Institutes of Health postdoctoral research fellow in digestive diseases epidemiology and functional GI disorders, and later as a clinical fellow in gastroenterology and hepatology.

Session 4

Faculty Financial Disclosure Statements The presenting faculty reports the following: Dr Cash receives Consulting fees from Zx Pharma; Medical Advisory Board fees from Forest, Ironwood, Paion, Salix, and Takeda; Speakers Bureau honorarium from Forest, Ironwood, Salix, and Takeda.

Dr Dorn is an ad hoc consultant to investors and marketers.

Education Partner Financial Disclosure Statement The content collaborators at Miller Medical Communications, LLC have no financial relationships to disclose.

Suggested Reading List Brandt LJ, Chey WD, Foxx-Orenstein AE, et al; for the American College of Gastroenterology Task Force on Irritable Bowel Syndrome. An evidence-based position statement on the management of irritable bowel syndrome. Am J Gastroenterol. 2009;104 (Suppl 1):S1-S35. Canavan C, West J, Card T. The epidemiology of irritable bowel syndrome. Clin Epidemiol. 2014;6:71-80. Chey WD, Maneerattaporn M, Saad R. Pharmacologic and complementary and alternative medicine therapies for irritable bowel syndrome. Gut Liver. 2011;5(3):253-266. Drossman DA, Morris CB, Schneck S, et al. International survey of patients with IBS: symptom features and their severity, health status, treatments, and risk taking to achieve clinical benefit. J Clin Gastroenterol. 2009;43(6):541-550. Engsbro AL, Begtrup LM, Kjeldsen J, et al. Patients suspected of irritable bowel syndrome--cross-sectional study exploring the sensitivity of Rome III criteria in primary care. Am J Gastroenterol. 2013;108(6):972-980. Harkness EF, Harrington V, Hinder S, et al. GP perspectives of irritable bowel syndrome--an accepted illness, but management deviates from guidelines: a qualitative study. BMC Fam Pract. 2013;14:92. Jarrett ME, Cain KC, Burr RL, et al. Comprehensive self-management for irritable bowel syndrome: randomized trial of in-person vs. combined in-person and telephone sessions. Am J Gastroenterol. 2009;104(12):3004-3014. Jellema P, van der Windt DA, Schellevis FG, van der Horst HE. Systemic review: accuracy of symptom-based criteria for diagnosis of irritable bowel syndrome in primary care. Aliment Pharmacol Ther. 2009;30(7):695-706. Ladabaum U, Boyd E, Zhao WK, et al. Diagnosis, cormorbidities, and management of irritable bowel syndrome in patients in a large health maintenance organization. Clin Gastroenterol Hepatol. 2012;10(1):37-45. Lee V, Guthrie E, Robinson A, et al. Functional bowel disorders in primary care: factors associated with health-related quality of life and doctor consultation. J Psychosom Res. 2008;64(2):129-138. Lembo AJ, Conboy L, Kelley JM, et al. A treatment trial of acupuncture in IBS patients. Am J Gastroenterol. 2009;104(6):1489-1497. Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology. 2006;130(5):1480-1491. MacPherson H, Tilbrook H, Bland JM, et al. Acupuncture for irritable bowel syndrome: primary care based pragmatic randomised controlled trial. BMC Gastroenterol. 2012;12:150. McKenzie YA, Alder A, Anderson W, et al. British Dietetic Association evidence-based guidelines for the dietary management of irritable bowel syndrome in adults. J Hum Nutr Diet. 2012;25(3):260-274. National Institute for Health and Care Excellence (NICE). Irritable bowel syndrome in adults: diagnosis and management of irritable bowel syndrome in primary care. February 2008;CG61. Accessed January 30, 2015.

Session 4

Rao S, Lembo AJ, Shiff SJ, et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. Am J Gastroenterol. 2012;107(11):1714-1724. Spiegel BM, Farid M, Esrailian E, Talley J, Chang L. Is irritable bowel syndrome a diagnosis of exclusion? A survey of primary care providers, gastroenterologists, and IBS experts. Am J Gastroenterol. 2010;105(4):848-858. Wilkins T, Pepitone C, Alex B, Schade RR. Diagnosis and management of IBS in adults. Am Fam Physician. 2012;86(5):419-426. Yoon SL, Grundmann O, Koepp L, Farrell L. Management of irritable bowel syndrome (IBS) in adults: conventional and complementary/alternative approaches. Altern Med Rev. 2011;16(2):134-151.

SESSION 412:30 – 1:45pm

Optimizing the Diagnosis, Treatment, and Management of Irritable Bowel Syndrome

SPEAKERSBrooks D. Cash, MD

Spencer Dorn, MD, MPH, MHA

Presenter Disclosure Information

►Dr Cash receives Consulting fees from Zx Pharma; Medical Advisory Board fees from Forest, Ironwood, Paion, Salix, and Takeda; Speakers Bureau honorarium from Forest, Ironwood, Salix, and Takeda.

►Dr Dorn is an ad hoc consultant to Gerson Lehrman Group, Guidepoint Global and Coleman Research Group.

The following relationships exist related to this presentation:

Off-Label/Investigational Discussion

► In accordance with pmiCME policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations.

Learning Objectives

After participating in this educational activity the participant should be able to:

• Diagnose IBS and differentiate from other bowel disorders using established clinical guidelines

• Summarize the efficacy and safety of pharmacologic and nonpharmacologic treatment options for IBS

• Implement patient-specific methods for managing IBS symptoms and improving function and quality of life

3

4

Generic Name Trade Name 

Alosetron Lotronex

Amitriptyline Elavil, Endep, Vanatrip

Cholestyramine Cholestyramine Light, Prevalite, Questran, Questran Light 

Citalopram CeleXA

Desipramine Norpramin

Dicyclomine Bentyl

Diphenoxylate‐atropine Lomotil

Doxepin Adapin, Silenor, Sinequan

Elobixibat Elobixibat

Eluxadoline Eluxadoline

Fluoxetine Prozac, Sarafem

Hyoscyamine Anaspaz, Cystospaz, Donnamar, Levsin

Imipramine Tofranil, Tofranil‐PM

Generic Name Trade Name 

Ispaghula Fybogel, Ispagel

Linaclotide  Linzess

Loperamide Imodium, Imodium A‐D, Kaopectate II, Maalox Anti‐Diarrheal Caplets, Pepto Diarrhea Control

Lubiprostone Amitiza

Mesalamine/Mesalazine Apriso, Asacol, Lialda, Pentasa

PEG 3350+E  Colyte, GaviLyte‐C, GolytelyGlycoLax,MiraLax

Paroxetine Paxil, Paxil CR, Pexeva

Plecanatide Plecanatide

Prucalopride Resolor

Psyllium Konsyl, Metamucil, Reguloid

Rifaximin Xifaxan

Brooks D. Cash, MDProfessor of MedicineUniversity of South AlabamaMobile, Alabama

10

Worldwide prevalence: 7% to 10%

1.5 times more prevalent in women

More commonly diagnosed in patients <50 years of age

More common in lower socioeconomic groups

Patients with IBS have more physician visits, hospitalizations, missed workdays, prescriptions, and diagnostic tests than those without

11

IBS=irritable bowel syndrome.

12

Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis

Onset associated with a change in frequency of 

stool

Onset associated with a change in form of stool

Recurrent abdominal pain or discomfortat least 3 days/month in the last 3 months

associated with ≥2 of the following:

Improvement with defecation

Additional IBS “testing,” including routine laboratory tests and colonoscopy, unnecessary unless alarm features present

13

IBS-C IBS-M

IBS-U IBS-D

100

75

50

25

0

0 25 50 75 100

Loose or watery stools (%)

Hard or Lumpy Sto

ols (%)

IBS‐C: Constipation‐predominant IBS

IBS‐D: Diarrhea‐predominant IBS

IBS‐M: Mixed IBS (hard and loose stools over periods of weeks and months)

IBS‐U: Unsubtyped IBS

Abdominal pain – 29% state this is the predominant symptom

Misinformation 15% believe IBS will turn into cancer 30% believe IBS increases risk for IBD 17% believe IBS will lead to malnutrition

Lack of information Prevalent physician belief IBS due to anxiety (80.5%) or 

depression (63.2%) Only 2/3 of patients recognize that IBS does not shorten

life expectancy

14

LemboT et al. Am J Gastroenterol. 1999;94(5):1320–1326. ; Lacy et al. Am J Gastroenterol. 2005;100(s9):S324; Noddin et al. Am J Gastroenterol. 2005;100(s9):S323; Lee et al. Am J Gastroenterol. 2005;100(s9):S336.

IBD=inflammatory bowel disease.

Enteric nervous system dysfunction Gastrointestinal 

dysmotility Visceral hypersensitivity

Disordered CNS pain processing

Post‐infectious

Small intestinal bacterial overgrowth Dysbiosis

Food intolerance

Genetics

Mast cell dysfunction

Somatization

CNS=central nervous system.

18

Gastrointestinal

Colorectal cancer

Diverticular disease

Gynecologic

Ovarian cancer Endometriosis

Drugs

Opiates

Anticholinergics

Antidepressants

Metabolic/Endocrine

Hypothyroidism

Diabetes

Neurologic

Parkinson disease

Multiple sclerosis

Autonomic neuropathy

Other

Amyloidosis

Scleroderma

19

Dietary factors

Lactose Gluten Other FODMAPs

Drugs

Infection

Giardiasis Amebiasis C difficile

Malabsorption

Celiac disease

Inflammatory bowel disease

Crohn’s disease Ulcerative colitis Microscopic colitis

Psychological

Panic disorder Somatization Depression

FODMAPs=fermentable oligosaccharides, disaccharides, monosaccharides, and polyols.

20

IBS is a syndrome—a collection of symptoms

Diagnosis possible via a thorough history of symptoms and physical examination

Because symptoms are non‐specific, must consider alternative organic diagnoses

Serious organic illnesses typically produce alarm symptoms (eg, bleeding, weight loss, etc)

21

302 Danish patients aged 18‐50 years referred from  primary care. No alarm features. Randomized to:

▪ Exclusionary strategy: Blood work, stool samples, lower endoscopy with biopsy

▪ Positive strategy: CBC and CRP only

Followed for 1 year

No difference in any outcome measure (symptoms, HRQL, use of health care resources, etc)

No cases of IBD, CRC, or celiac disease identified

Exclusionary strategy more expensive▪ Direct costs: $863 greater▪ Mean total costs: $1915 greater

Begtrup LM et al. ClinGastroenterol Hepatol. 2013;11(8):956‐962.

CBC=complete blood count; CRC=colorectal cancer; CRP=C‐reactive protein; HRQL=health‐related quality of life.

22

8

72

Co

nsi

der

IB

S a

Dia

gn

osi

s o

f E

xclu

sio

n,

%

IBS Experts(n=27)

Community Clinicians(n=281)

Clinicians who believed IBS was a diagnosis of exclusion ordered 1.6 times more tests and spent $364more on diagnostic tests per patient (P<.0001)

Clinicians who believed IBS was a diagnosis of exclusion ordered 1.6 times more tests and spent $364more on diagnostic tests per patient (P<.0001)

23

Histologic Findings in IBS Patients and Controls;Populations Not Matched for Age or Sex

LesionIBS Patients

n=466 (%)

Controlsn=451 (%)

P Value

Adenomas 36 (7.7) 118 (26.1) <.0001

Hyperplastic polyps 39 (8.4) 52 (11.5) NS

Cloorectal adenocarcinoma 0 (0.0) 1 (0.2) NS

IBD 2 (0.4) 0 (0.0) NS

Microscopic colitis 7 (1.5) N/A N/A

Microscopic colitis was more common in a subset of patients with IBS‐D who were ≥45 years (2.3%).

N/A, not applicable; NS=not significant.

24

There is a paucity of evidence guiding radiologic imaging in IBS

Imaging study should be influenced by predominant symptoms

Data suggest very low yield of CT and U/S

Definitive recommendations must await further research

O’Connor OJ et al. Radiology. 2012;262(2):485‐494.

U/S=ultrasonography.

25 26

Up to 10% of chronic idiopathic abdominal pain Entrapment of anterior cutaneous branch of thoracic intercostal nerve

Sharply localized pain and superficial tenderness  + Carnett sign: accentuated localized tenderness with abdominal wall tensing

Reassurance and avoidance of precipitating causes often sufficient

Anesthetic/corticosteroid injection effective in ≈ 75%▪ Also serves as diagnostic confirmation

Srinivassan R, et al. Am J Gastroenterol. 2002;3(4):824‐30.

27

1% of the adult population; 25% of those diagnosed with IBS‐D

Tests that directly assess bile acid malabsorption (SeHCAT, 14C‐glycocholate breath tests, serum C4, fecal bile acids) either not available in United States or not validated

Therapeutic trial only option Bile acid sequestrants

Vijayvargiya P et al. ClinGastroenterol Hepatol. 2013;11(10):1232‐1239.

SeHCAT= 75selenium homotaurocholic acid test.

28

Crohn’s disease, ulcerative colitis, undifferentiated IBD

IBS symptoms ARE common in IBD patients in “remission” 

35% overall; higher in Crohn’s disease 

Opinion divided as to what they mean

Unrecognized [latent] IBD

Real or coincident IBS; linked to psychosocial issues

29

Halpin SJ, et al. Am J Gastroenterol. 2012;107(10):1474‐1482.Keohane J et al. Am J Gastroenterol. 2010;105(8):1789‐1794. Quigley EM, et al. Am J Gastroenterol. 2012;107(10):1483‐1485. Vivinus‐NébotM et al. Gut. 2014;63(5):744‐752.Jonefjäll B et al. Neurogastroenterol Motil. 2013;25(9):756‐e578 Berrill JW et al. Aliment PharmacolTher. 2013;38(1):44‐51.

“Post‐diverticulitis IBS” 2204 subjects at Los Angeles Veterans Administration medical center 

who had an episode of diverticulitis and followed for 6.3 years▪ Almost 5 times more likely to be diagnosed with IBS later

Symptomatic uncomplicated diverticular disease (SUDD) 229 treated with mesalazine ± L casei vs L casei alone vs placebo for 10 

days per month for 12 months▪ Higher remission rates in treatment groups▪ Symptomatic diverticulitis in 6 on placebo and 1 in probiotic group

345 patients with uncomplicated diverticulitis

Mesalamine 3 g daily vs placebo for 48 weeks  % recurrence‐free at 48 weeks: 68% mesalamine, 74% placebo

30Cohen E et al. ClinGastroenterol Hepatol. 2013;11(12):1614‐1619.TursiA. et al. DDW 2013. KruisW. et al. DDW 2013

General Practice Research Database in the United Kingdom Celiac patients were 3 times more likely to have a prior 

diagnosis of IBS, even for 10 years previously

38% of celiac disease patients have IBS symptoms; especially if non‐adherent with gluten free diet

Should you screen for celiac disease? YES

Mohseninejad L et al. Eur J Health Econ. 2013;14(6):947‐957.

NOCash BD et al. Gastroenterology. 2011;141(4):1187‐1193.

31Card TR et al. Scand J Gastroenterol. 2013;48(7):801‐807. Sainsbury A et al. ClinGastroenterol Hepatol. 2013;11(4):359‐365.

IBS patients (physician diagnosis)Positive for both tTGA and EMACeliac disease not biopsy‐proven

Non‐constipated IBS patients (Rome II)Biopsy‐proven celiac disease

32

Case‐Control Study Prospective Study

0.5

1

0

0.2

0.4

0.6

0.8

1

1.2

1.4

Patients w

ith celiac 

disease (%)

0.4 0.4

0

0.2

0.4

0.6

0.8

1

1.2

1.4

Patients w

ith celiac 

disease  (%)  

N=566N=555

Controls IBS Patients

Saito‐Loftus Y, et al. Am J Gastroenterol. 2008;103(suppl 1):S472. Abstract 1208;  Cash BD et al. Gastroenterology. 2011;141(4):1187‐1193.

N=492N=458

Controls IBS Patients

P=NS P=NS

Prospective study: 7.3% IBS and 4.8% controls had at least 1 abnormal gluten‐directed serology (most often IgG AGA)

Adapted from Verdu EF et al. Am J Gastroenterol. 2009;104(6):):1587‐1594.

CD=celiac disease. 33

IBS symptoms Spectrum of CD

Is it IBS, Celiac Disease or Something in Between? 

Motility / visceral sensationBrain – gut interactionsImmune activationAltered gut microbiome

Potential / asymptomatic CD

Symptomatic CD

Non‐celiac glutenor

wheat sensitivity

Routine laboratory tests: CBC, CMP, TSH, stool O&P, abdominal imaging  not recommended

Serologic testing for celiac disease (IBS‐D/M) 

strongly consider

Lactose breath testing  selected cases

Colonoscopy  recommended if ≥50 years of age, with biopsies in refractory IBS‐D (to exclude microscopic colitis)

ACG=American College of Gastroenterology; CMP=Comprehensive Metabolic Panel; TSH=thyroid‐stimulating hormone.

American College of Gastroenterology Task Force on Irritable Bowel Syndrome; Brandt LJ et al. Am J Gastroenterol. 2009;104 suppl 1:S1‐S35. 34

Refractory or worsening abdominalsymptoms

Older patient (≥50 years of age;≥45 years of age if black) at onset

Blood in stools (hematochezia)

Anemia

Weight loss (unintentional)

Anorexia

Family history of organic GI disease

Further investigation warranted

35

Only 1% to 9% with IBS diagnosed with an alternative organic GI disorder after 30 years of follow‐up 

Long‐term follow‐up: 2% to 18% worse, 30% to 50% of patients unchanged 

Prior surgery (1 study), higher somatic scores (1 study), higher baseline anxiety (2 studies), depression (1 study) predicted worse symptoms during long‐term follow‐up 

Short duration and constipation: better outcome                                 

El‐Serag HB et al. Aliment PharmacolTher. 2004;19(8):861‐870.36

Identify IBS symptoms, presence of alarm features

Meets criteria, no alarm features make diagnosis of IBS

Does not meet criteria, has alarm features look for alternative diagnosis

Symptomatic treatment for predominant symptoms

Assess response to treatment

Good response  continue Rx Poor response  reassess

LongstrethGF et al. Gastroenterology. 2006;130(5):1480‐1491; Erratum in: Gastroenterology. 2006;131(2):688; American College of Gastroenterology Task Force on Irritable Bowel Syndrome; Brandt LJ et al. Am J Gastroenterol. 2009;104 suppl 1:S1‐S35.

Poor response  reassess

37

Spencer Dorn, MD, MPH, MHAUniversity of North Carolina School of MedicineChapel Hill, North Carolina

38

Patient‐Provider relationship

Lifestyle changes

Diet, fiber, and probiotics

CAM therapies

Antispasmodics

Antidepressants 

Psychological therapies

Gut‐specific

IBS‐D: Alosetron IBS‐C: PEG, Lubiprostone, Linaclotide

CAM, complementary and alternative medicine; IBS-C, irritable bowel syndrome with constipation; IBS-D, irritable bowel syndrome with diarrhea; PEG, polyethylene glycol.

39

“Cornerstone of treatment” Listen actively Determine reasons for visit Identify and respond to 

concerns and expectations Educate thoroughly Set realistic expectations Involve the patient in the treatment

Positive physician‐patient interaction reduces health care utilization and increases patient satisfaction

Drossman DA et al. Gastroenterology. 2002;123(6):2108-2131.; Owens DM et al. Ann Intern Med. 1995;122(2):107-112.Dorn SD et al, Clin Gastroenterol Hepatol. 2011;9(12):1065-1071.

40

Diary card symptom tracking can help identify exacerbating and alleviating factors and increase sense of control

Moderate exercise for 20 to 60 minutes x 3 to 5 days/week improves IBS symptoms

Johannesson E et al. Am J Gastroenterol. 2011;106(5):915-922.41

Among patients with IBS, diet is the#1 topic of interest

60% of subjects report that symptoms worsen after meals

The act of eating as well as the specific    foods consumed may be one of many    factors that influences IBS

Studying diet is quite challenging

True food allergies are very rare

General recommendations are possible,       but diet should be tailored to the  individual

Halpert A et al. Am J Gastroenterol. 2007;102(9):1972-1982.; Simrén M et al. Digestion. 2001;63(2):108-115.; CremoniniF,; Camilleri M. Gut. 2003;52(5):619-621.; Dainese R et al. Am J Gastroenterol. 1999;94(7):1892-1897. 42

Excess Fructose

Honey, apples, pears, peaches, mangos, fruit juice, dried fruit

LactoseMilk, ice cream, cheese,whey, curd

FructansWheat (large amounts), rye (large amounts), onions, leeks, zucchini

SorbitolApricots, peaches, artificial sweeteners and gums

RaffinoseLentils, cabbage, Brussels sprouts, asparagus, green beans, legumes

Fermentable Oligo‐, Di‐, Monosaccharides And Polyols 

43

RCTs NResponse*

Fiber             Placebo    

RR of Unimproved Symptoms(95% CI)

NNT(95%CI)

Overall 12 591 48%                 43% 0.87 (0.76‐1.0) 11 (5‐100)

Soluble 6 321 48%                 36% 0.78 (0.63‐0.96) 6 (3‐50)

Insoluble 5 221 46% 46% 1.02 (0.82‐1.27)

*Improved or resolved symptoms.

CI, confidence interval; NNT, number needed to treat; RCTs, randomized, controlled trials; RR, relative risk.

46

Probiotics: live or attenuated microorganisms that have beneficial effects in humans

Meta‐analysis of 35 RCTs (n=3452) determined: “Probiotics are effective therapies for IBS” (global symptoms, pain, bloating, and gas) (NNT=7)

“We found evidence to support the use of combinations of probiotics as a group, although not for any of the different combinations studied individually.”

47

Up to 50% of all patients with IBS use some sort of CAM

Few CAM therapies have been rigorously evaluated for IBS:   Peppermint – Safe and moderately efficacious for pain Acupuncture – Real and sham both more efficacious than 

placebo

48

Smooth muscle relaxants with other anticholinergic effects Examples: dicyclomine, hyoscamine

Meta‐analysis of 22 RCTs comparing 12 different antispasmodics vs placebo (n=1778 patients) Significant heterogeneity among studies

Symptoms persist in 39% of patients receiving antispasmodics vs 56% of placebo‐treated patients (RR: 0.68; 95% CI: 0.57‐0.81)

Appear most useful for abdominal pain

Overall, these agents are cheap, widely available, and moderately efficacious for treating pain and bloating (and, possibly, urgency)

Ford AC et al. BMJ. 2008;337:b1881. 49

Tricyclic Antidepressants (TCAs): 9 studies (N=319 drug vs 256 control) Imipramine*, desipramine*, amitriptyline*, doxepin*; doses 10‐150 mg Meta‐analysis favors treatment

Selective Serotonin Reuptake Inhibitors (SSRIs): 5 studies (N=113 drug vs 117 control) Fluoxetine*, paroxetine*, citalopram*; dose 10‐40 mg Meta‐analysis favors treatment 

Putative mechanisms include: Central effects (antinociception, +/‐ anxiolysis and antidepressive)  Peripheral effects (SSRIs reduce gut transit, TCAs are modestly 

anticholinergic) 

Anecdotally, it is essential to (a) discuss the rationale for these medications, (b) explain that patients may not see benefits for 4 to 6 weeks and that the dose may need to be adjusted

Ford AC et al. Gut. 2009;58(3):367-378.

*These agents are not currently US Food and Drug Administration approved for IBS.50

RR NNTTrials N 95% CI 95% CI

Cognitive behavioral 7 491 0.60 3therapy  0.42‐0.87 2‐7

Relaxation  5 234 0.82

training  0.63‐1.08

Dynamic  2 273 0.60 3.5psychotherapy  0.39‐00.93 2‐25

Hypnotherapy 2 40 0.48 20.26‐0.87 1.5‐7

Anecdotally, it is critical to (a) identify appropriate candidates and (b) explain the rationale for psychological therapy

Ford AC et al. Gut. 2009;58(3):367-378.51

Study NFemale 

%Response: 

Alosetron, %Response: Placebo, %

Therapeutic

Gain, %

Camilleri1 370 53 60 33 27

Camilleri2 647 100 41 29 12

Camilleri3 626 100 43 26 17

Lembo4 801 100 73 57 16

Jones5 623 100 58 48 10

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Female patients with chronic, severe IBS‐Dwho failed other treatments

Patient education regarding possible serious adverse effects of severe constipation or ischemic colitis

0.95 cases of ischemic colitis/1000 patient‐years

0.36 cases of severe constipation/1000 patient‐years

If ischemic colitis occurs, it is usually within the first month of therapy 

Prescribing program mandated by US Food and Drug Administration 

Requires patient to sign attestation form

53

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

# SBMs Pain Level

Placebo (n=71)

PEG 3350+E (n=68)

PEG is an alcohol that is not absorbed through the gut lumen.  It creates an osmotic gradient that drives water into the lumen

139 adults with IBS‐C were randomized to placebo or PEG 3350 plus electrolytes (PEG 3350+E)

During week 4 of treatment, PEG improved number of SBMs (P<.0001), but not pain in IBS‐C patients

SBMs, spontaneous bowel movements.

54

12‐week treatment period

Overall responder: Monthly responder for at least 2 of 3 months

Monthly responder: At least moderate relief for 4/4 weeks or significant relief for 2/4 weeks

Ov

era

ll R

es

po

nd

ers

(%

)

n=387n=780

Lubiprostone8 µg bid 

Placebo

*P=.001

17.9

10.1

0

25

50

Drossman DA et al. Aliment Pharmacol Ther. 2009;29(3):329-341. 56

Mean SBM Frequency per Month

8

7

6

5

4

3

2

1

01 2 3 4 5 6 7 8 9 10 11 12 13Baseline

Phase 3Studies

RandomizedWithdrawal/Extension Studies

Month of Treatment

Abdominal Pain/Discomfort

‐0.25

Month of Treatment

13121110987654321

‐0.50

‐0.75

‐1.00

‐1.25

‐1.50

Change From Base

line

P/L Group(n=179)

L/P/L Group(n=80)

L/L Group(n=261)

N=520 IBS‐C patients who completed 12 or 16 weeks of a placebo‐controlled phase 3 trial;patients enrolled in the extension study all received lubiprostone 8 µg bid.

P, placeboL, lubiprostone57

Most common AE diarrhea (19.7% vs 2.5%)

Chey WD et al. Am J Gastroenterol. 2012;107(11):1702-1712.

49.1

25.1

0

20

40

60

80

Lin 290 mcg Placebo

% A

deq

uat

e R

elie

f: IB

S S

ymp

tom

s

*P<.0001NNT=4.2

N=403N=401

AE, adverse event.

58

Patient‐Provider relationship

Lifestyle changes

Diet, fiber, and probiotics

CAM therapies

Antispasmodics

Antidepressants 

Psychological therapies

Gut‐specific IBS‐D: Alosetron IBS‐C: PEG, Lubiprostone, Linaclotide

60